Disturbances of iron homeostasis can have significant clinical consequences. Iron deficiency is the world's most prominent nutritional deficiency and anemia of chronic disease (ACD) from decreased intestinal iron absorption and impaired iron release from macrophages is common in hospitalized patients. The overall aim of this study is to help us understand the genetic basis of variation in iron metabolism between people. Inbred mice show significant variation in multiple traits including iron metabolism. We propose to identify loci underlying strain specific differences in iron metabolism through a combination of in silico SNP association and gene expression profiling. We will test candidate genes for iron related function in Zebrafish, a complementary vertebrate model. Finally, we will assess candidate genes for a role in human iron metabolism through population based studies. We have assembled a multi- disciplinary research team of iron metabolism biologists, geneticists and computational biologists to carry out the proposed study. PUBLIC HEALTH RELEVANCE: Anemias from iron deficiency or chronic disease are common disorders. The overall aim of this study is to improve our understanding of iron metabolism and its variation between people in order to develop more effective therapies for these diseases.